Molecular tools for Bunyavirus antiviral screening

用于布尼亚病毒抗病毒筛选的分子工具

• 批准号: 6918777
• 负责人: Paul David Olivo
• 金额: $ 41.37万
• 依托单位: APATH, LLC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6918777
• 关键词: Bunyaviridae; Crimean Congo hemorrhagic fever virus; DNA directed RNA polymerase; Hantavirus; Rift Valley fever virus; Sin Nombre virus; antiviral agents; biotechnology; bioterrorism /chemical warfare; chemical registry /resource; drug discovery /isolation; drug screening /evaluation; enzyme inhibitors; gene expression; high throughput technology; hydrolase; mycophenolic acid; replicon; reporter genes; ribavirin; small molecule; technology /technique development; virus genetics; virus replication

DESCRIPTION (provided by investigator): Several viruses in the family Bunyaviridae are significant human pathogens and potential agents of bioterrorism. Vaccines against some of these viruses do exist, but with the exception of ribavarin, there are no broad-spectrum antiviral compounds capable of inhibiting replication of more than one member of the family. Using LaCrosse virus (LAC) as a prototype virus for the family, we plan to develop a combination of infection-dependent and infection-independent screening tools and to initiate a screen for compounds with anti-bunyavirus activity. The screening tools will be based on virus promoter-driven reporter gene constructs generated by bacteriophage T7 RNA polymerase or mammalian RNA polymerase I. Similar systems have been developed and utilized for other negative strand viruses including respiratory syncytial virus, Ebola virus, and influenza A virus. We plan to use the LAC infection-independent system in an automated, high throughput screening program to identify small molecule antiviral compounds. Compounds that exhibit antiviral activity will be tested for effectiveness against LAC-infected cells. Active compounds will then be assessed for broad-spectrum antiviral activity using virus promoter driven reporter genes derived from the bunyaviruses Hantaan (NIAID category A agent), Sin Nombre (NIAID category A agent), Rift Valley Fever (NIAID Category A agent) and Crimean Congo Hemorhagic Fever (NIAID category C agent). Given that LAC is a NIAID Category C agent completion of this application should identify antiviral compounds active against one and perhaps several NIAID priority pathogens. The combination of high throughput screening, rapid virus specific readouts of infectivity and available BSL2/BSL3 space make this application an attractive prototype for screening of broad spectrum antimicrobial compounds with other NIAID priority pathogens.

描述（研究人员提供）：Bunyaviridae家族中的几种病毒是生物恐怖主义的重要人类病原体和潜在的药物。确实存在针对其中一些病毒的疫苗，但是除了利巴巴林外，没有能够抑制多个家庭成员复制的广谱抗病毒化合物。我们计划使用曲棍网er病毒（LAC）作为家族的原型病毒，我们计划开发依赖感染和无感染的筛查工具的组合，并启动筛选抗基孔病毒活性的化合物。筛选工具将基于由病毒启动子驱动的报告基因构建体由噬菌体T7 RNA聚合酶或哺乳动物RNA聚合酶I产生的基因构建体I.已开发并用于其他阴性链病毒，包括呼吸道综合病毒，Ebola病毒，Ebola病毒，Ebola病毒，以及Impalza a verus。我们计划在自动化的高吞吐量筛选程序中使用与lac感染无关的系统来识别小分子抗病毒化合物。表现出抗病毒活性的化合物将进行测试，以确保对lac感染细胞的有效性。然后，将使用源自Bunyaviruses Hantaan（NIAID类别A特工），Sin Nombre（NIAID A类代理），Rift Valley Fever（NIAID类别）（NIAID A Agent）和Crimean Congo Congo Congo Hemorhagic Fever（NIAID类别）（NIAID类别A代理商）（NIAID类别A代理），使用启动子驱动的记者基因来评估活性化合物的广谱抗病毒活性。鉴于LAC是本应用程序的NIAID类别C代理的完成，应针对一种或可能的几种NIAID优先病原体识别抗病毒化合物。高吞吐量筛查，感染性的快速病毒特异性读数和可用的BSL2/BSL3空间的组合使该应用成为筛选与其他NIAID优先病原体的宽光谱抗菌化合物的有吸引力的原型。